Background

Methods

We tested whether passive immunization with polyclonal IgG raised in rhesus monkeys (RMs) with chronic clade C SHIV infection, termed SHIVIG, could protect RMs against multiple low-dose intrarectal challenges with the R5 tier-2 SHIV-2873Nip carrying an HIV clade C envelope heterologous to the viruses/envelopes against which the IgG responses had been elicited. We compared in vitro SHIVIG characteristics with in vivo protection.

Four groups of RMs were given SHIVIG at different doses: Group 1 (400 mg/kg), Group 2 (675 mg/kg), Group 3 (25 mg/kg) and Group 4 (none; virus-only control) followed by weekly low-dose challenges with SHIV-2873Nip. All controls and all SHIVIG-treated animals became systemically infected. RMs given 400 mg/kg of SHIVIG showed significantly lower peak viral RNA loads compared to controls. Surprisingly, single-genome analysis revealed a significant increase in the number of transmitted variants in Group 3 compared to controls (P=0.032), suggesting increased acquisition. Complement-mediated Ab-dependent enhancement of infection (C’-ADE) at low SHIVIG concentrations was observed in vitro.

Conclusion

Lack of protection and possibly increased acquisition has been reported for a passive immunization study that tested the efficacy of HIV hyperimmune globulin in preventing infection in Ugandan infants born to HIV-positive women (Onyango-Makumbi, JAIDS 2011). Thus, our primate model data paralleled clinical phase III results and suggest that polyclonal anti-HIV-1 Abs play a dual role upon virus encounter.